Folate Deficiency Associated with Gene Modulation

Folate deficiency has been associated with the onset of varied metabolic abnormalities, “including insulin resistance, by altering epigenetic processes on key regulatory genes,” such as the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2). CAMKK2 is part of the calcium-triggered signaling cascade, and influences obesity and glucose metabolism.

This study looked at subjects with a total folate intake lower than 300 ug/d, more “fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1, and compared [these levels] to those consuming greater than 300 ug/d [of folate].” They determined that “folate deficiency was related to lower CAMKK2 methylation.

In conclusion, this summary proposed “associations between low folate intakes, lower CAMKK2 gene methylation, and insulin resistance in obese individuals.”

My Take:
I know this reads as pretty technical, but it is the “dummied down” version. So, let me define some terms for you.

Epigenetics is the study of gene expression rather than gene composition. The term literally translates as “above genetics.”

Folate is the food form of folic acid, one of the B vitamins involved in hundreds of metabolic pathways in the human body. However, folate cannot be used by the body in its’ food form. It must have a ‘methyl’ group attached to it through a process called methylation.

I have written frequently about variations in genetic snippets that impair methylation of folate. However, this study shows impaired gene expression from a dietary deficiency of folate that contributes to metabolic syndrome.

Folate, translated as ‘foliage’ is found in all dark green leafy vegetables. Most Americans are deficient in their daily intake because they just don’t eat any vegetables. I recommend five servings of veggies daily and count a big salad as two servings.

The Bottom Line:
This study illuminates some of the biochemistry, including genetic expression, that links poor dietary habits to diabetes and heart disease. While supplementation of bioavailable folic acid is a common occurrence in my practice, it does not replace a healthy diet.

Source: Nutrition Research, February 2018